A Porous Au@Rh Bimetallic Core–Shell Nanostructure as an H2O2‐Driven Oxygenerator to Alleviate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

Abstract In treatment of hypoxic tumors, oxygen‐dependent photodynamic therapy (PDT) is considerably limited. Herein, a new bimetallic and biphasic Rh‐based core–shell nanosystem (Au@Rh‐ICG‐CM) is developed to address tumor hypoxia while achieving high PDT efficacy. Such porous Au@Rh core–shell nanostructures are expected to exhibit catalase‐like activity to efficiently catalyze oxygen generation from endogenous hydrogen peroxide in tumors. Coating Au@Rh nanostructures with tumor cell membrane (CM) enables tumor targeting via homologous binding. As a result of the large pores of Rh shells and the trapping ability of CM, the photosensitizer indocyanine green (ICG) is successfully loaded and retained in the cavity of Au@Rh‐CM. Au@Rh‐ICG‐CM shows good biocompatibility, high tumor accumulation, and superior fluorescence and photoacoustic imaging properties. Both in vitro and in vivo results demonstrate that Au@Rh‐ICG‐CM is able to effectively convert endogenous hydrogen peroxide into oxygen and then elevate the production of tumor‐toxic singlet oxygen to significantly enhance PDT. As noted, the mild photothermal effect of Au@Rh‐ICG‐CM also improves PDT efficacy. By integrating the superiorities of hypoxia regulation function, tumor accumulation capacity, bimodal imaging, and moderate photothermal effect into a single nanosystem, Au@Rh‐ICG‐CM can readily serve as a promising nanoplatform for enhanced cancer PDT.